Salk scientists develop drug that slows Alzheimer's in mice

Salk scientists developed J147, a synthetic drug
shown to improve memory and prevent brain
damage in mice with Alzheimer's disease.

According to the Alzheimer's Associat ion, more than
5 million Americans are living with Alzheimer's disease, the sixth leading
cause of death in the country. Despite years of research, there are no
disease-modifying drugs for the condition. Current FDA-approved
medications, including Aricept, Razadyne and Exelon, offer only fleeting
short-term benefits for patients and do nothing to slow the irreversible
decline of brain function that characterizes the disease.

A drug developed by scientists in the lab of David Schubert, however,
reverses memory deficits and slows Alzheimer's disease in aged mice
following short-term treatment. The findings, published in Alzheimer's
Research and Therapy, may pave the way to a new treatment for
Alzheimer's disease in humans.

In developing the drug, known as J147, Schubert and his colleagues
bucked the trend within the pharmaceutical industry, which has focused
on the biological pathways involved in the formation of amyloid plaques,
the dense deposits of protein that characterize the disease. Instead, the
team used living neurons grown in laboratory dishes to test whether their
new synthetic compounds, which are based upon natural products derived
from plants, were effective at protecting brain cells against several
pathologies associated with brain aging. From the test results of each
chemical iteration of the lead compound, they were able to alter their
chemical structures to make them much more potent.

To test the efficacy of J147 in a much more rigorous preclinical
Alzheimer's model, the team then treated mice using a therapeutic
strategy that they say more accurately reflects the human symptomatic
stage of Alzheimer's. Administered in the food of 20-month-old genetically
engineered mice, at a stage when Alzheimer's pathology is advanced,
J147 rescued severe memory loss, reduced soluble levels of amyloid,
and increased neurotrophic factors essential for memory after only three
months of treatment. In a different experiment, the scientists tested J147
directly against Aricept, the most widely prescribed Alzheimer's drug, and
found that it performed as well or better in several memory tests.

Although J147 appears to be safe in mice, the next step will require
clinical trials to determine whether the compound will prove safe and
effective in humans, and Schubert and his team are currently seeking
funding for such a trial.